The effects of sex steroid hormones on two apolipoproteins (apoJ and apoE) implicated in the response to neurodegeneration and Alzheime~s disease will be examined in these experiments. Gonadectomy and steroid replacement will be used to control hormone levels in aging rats or rats undergoing synaptic remodeling caused by lesion models which mimic select aspects of Alzheimer's. In vitro models will also be used to study the mechanisms underlying the gene response to these hormones.